The association of chronic gingival inflammation with alveolar bone resorption has led to the presumption of a causal relation between these two processes; however, little is known of the factors or conditions which may mediate this relation. The objective of this proposal is to identify agents produced in chronic inflammation which may affect bone resorption. Bone resorbing activity will be assayed in a bone organ culture system which has been shown to respond to various agents which stimulate or inhibit resorption in vivo, such as parathyroid hormone, active metabolites of vitamin D, and calcitonin. Resorption will be quantitated by chemical and isotopic measurements of both mineral and matrix components as well as by histologic examination. Four approaches to the objective of this proposal will be undertaken as follows: 1. Continuation of studies already initiated on the secretion by cultured lymphocytes of agents which stimulate bone resorption; the kinetics of secretion; isolation and identification of the active agent(s) by column chromatography. 2. Studies on bone resorbing activity associated with specific components of the complement system. 3. Studies on the effects on bone resorption of isolated inflammatory cells, such as macrophages, polymorphonuclear leukocytes, lymphocytes, and mast cells or their products, added directly to bone cultures; development of microinjection methods for introducing these cells onto the endosteal surface of cultured bones. 4. Studies on bone resorbing factors which may be produced by cultured human gingival tissue; correlation of factors found with those isolated from studies on lymphocytes or complement. The pattern, time course, and type of resorption stimulated by factors found in any of these studies will be determined, as will their interactions with humoral stimulators and inhibitors of resorption.